Acute Tubular Injury With Vacuolization After Palbociclib Exposure in a Patient With Advanced Breast Cancer

Despite major advances in cancer therapy, including molecularly targeted agents and immunotherapies, patients remain at risk for drug-induced nephrotoxicity and organ damage from the underlying malignancy. Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have become an established therapeutic option for the patients with advanced hormone receptor-positive breast cancer. It is new class of drugs blocking the transition from the G1 to the S phase of the cell cycle, thereby preventing cell-cycle progression and tumor growth. Acute kidney injury (AKI) is not a well-described complication of CDK4/6 inhibitors. Pharmacologic studies suggest patients may have a rise in serum creatinine without true renal injury. Here, we report a biopsy-proven case of AKI associated with CDK4/6 inhibitor palbociclib.

Case Description. A 62-year-old woman with metastatic triple-positive breast cancer received paclitaxel, bevacizumab, and atezolizumab for two years to treat postoperative recurrence. Approximately one year after treatment initiation, she developed persistent proteinuria; however, her renal function remained stable, with a serum creatinine around 0.8 mg/dL (eGFR 51.3 - 60.4 mL/min/1.73m2). She had progression of disease, and treatment was switched to palbociclib. AKI was noted three weeks after palbociclib initiation, with a rise in serum creatinine from 0.84 mg/dL to 1.48 mg/dL. Cystatin C and 24-hour creatinine clearance also worsened to a similar level. Due to prior administration of atezolizumab up to three weeks ago, immune-related adverse events (irAE) were suspected, leading to initiation of prednisolone 60 mg/day. The patient was referred to our department for evaluation of AKI. No irAEs involving other organs were identified. Kidney biopsy revealed focal glomerular sclerosis (2 of 10 glomeruli) and global duplication of capillary loops with plasma protein leakage and subendothelial foam cells, suggesting chronic endothelial injury. Tubulointerstitial findings included approximately 10 % tubular atrophy and interstitial fibrosis with focal lymphocytic infiltrates. Proximal tubular epithelial cells exhibited fine cytoplasmic vacuolization, and obstruction of distal tubules by casts was suspected. Immunofluorescence demonstrated ribbon-like IgM staining along the capillary walls without definitive immune complex deposition on electron microscopy. Within proximal tubules, expanded vesicular structures, including autophagosomes and lysosomes, were observed. After discontinuation of palbociclib and gradual tapering of prednisolone over three months, renal function returned to baseline.

It is considered a case of acute tubular injury with cytoplasmic vacuolization following administration of a CDK4/6 inhibitor. CDK4/6 inhibition has been reported to impair autophagy, which may contribute to the observed tubular vacuolization and renal dysfunction. This case highlights a unique pattern of tubular injury potentially linked to autophagic disturbance caused by palbociclib.